Studies Provide Detailed Look at Treatment-Related Hyperkalemia

Rates of hyperkalemia associated with receipt of renin-angiotensin-aldosterone system inhibitors vary by age and comorbidities.

New study findings presented at the 55th European Renal Association-European Dialysis and Transplant Association congress in Copenhagen, Denmark, provide a more detailed look at hyperkalemia that develops in patients receiving renin-angiotensin-aldosterone system inhibitors (RAASi).

The studies show that the risk of RAASi-associated hyperkalemia varies by patient age and comorbidities, with chronic kidney disease (CKD) placing patients at the highest risk. One study characterized how hyperkalemia that develops in patients receiving mineralocorticoid receptor antagonists (MRA) impacts clinical management.

In a study of 434,027 patients receiving RAASi therapy, David T. Gilbertson, PhD, of the Chronic Disease Research Group in Minneapolis, and colleagues found that the overall rate of moderate and severe hyperkalemia was 1.3 episodes per 100 patient-years (PY). The rate increased from 0.8 episodes per 100 PY among patients aged 18 to 29 years to 2.4 per 100 PY for patients older than 80 years. The rates were 6.4 per 100 PY among patients with a history of hyperkalemia vs 0.6 per 100 PY among patients without such a history. The rates were 3.1, 2.5, and 11.5 per 100 PY among patients with diabetes, stage 4 chronic kidney disease (CKD), and stage 5 CKD, respectively.

The investigators defined moderate and severe hyperkalemia as potassium levels of 5.5–6.0 mmol/L and greater than 6.0 mmol/L, respectively.

A separate study of 13,726 new users of MRAs by Marco Trevisan, MS, of the Karolinska Institutet in Stockholm, Sweden, and colleagues found that within a year of starting treatment, 18.5% of them experienced at least 1 episode of hyperkalemia (potassium level greater than 5 mmol/L) detected, most within the first 3 months of therapy. CKD was associated with the greatest hyperkalemia risk, followed by older age, male sex, heart failure, peripheral vascular disease, diabetes, and concomitant use of ACE inhibitors, angiotensin-receptor blockers, and diuretics.

Among patients who experienced hyperkalemia, 47% discontinued MRA therapy and only 10% had their prescribed dose decreased. Discontinuation rates were higher following development of moderate/severe hyperkalemia (potassium level greater than 5.5 mmol/L) and early in therapy (less than months from initiation). In adjusted analyses, MRA discontinuation was most likely among patients with CKD. When MRA was discontinued, 76% of patients were not reintroduced to MRA therapy in the following year.